Astrakhan (Astarkhan/Hashtarkhan/Hajji Tarkhan), as a vital gateway at the mouth of the Volga River and on the shores of the Caspian Sea, played a key role in the evolution of commercial and political relations between Iran and Russia during the Safavid period. This study, employing a descriptive-analytical approach and based on library sources, examines the strategic position of this city within the Caspian regional trade network and its role in altering north-south trade routes. The findings indicate that the Russian capture of Astrakhan in 1556 CE and the opening of the Volga-Caspian route reduced the Safavids' dependence on passages under Ottoman control and strengthened the trade axis between Iran, Russia, and Europe. By becoming a permanent base for Iranian merchants, featuring the construction of dedicated caravanserais, and benefiting from the diplomatic support of both governments, this city turned into a primary hub for the exchange of silk, precious textiles, and other goods. The results of the present study show that Astrakhan not only served as a driving force for economic development and the deepening of Iran-Russia relations but also became a successful model of a multicultural and commercial city in the Caspian region.